Proceedings of The Physiological Society

University of Cambridge (2008) Proc Physiol Soc 11, PC115

Poster Communications

A comparison of the effects of capsazepine on type I and type II slowly adapting mechanoreceptors in the rat sinus hair follicle

P. M. Cahusac1, I. Sharma2

1. Department of Psychology, University of Stirling, Stirling, United Kingdom. 2. Department of Biological and Biomedical Sciences, Glasgow Caledonian University, Glasgow G4 0BA, Scotland, United Kingdom.

There is currently significant interest in determining the molecular bases for mechanotransduction in the vertebrate (Lumpkin & Caterina, 2007). We therefore tested a broad spectrum transient receptor potential (TRP) channel antagonist in an isolated sinus hair follicle preparation in which slowly adapting type I (St I) and type II (St II) could be distinguished. 28 adult Wistar-derived rats (mean weight 335 g) were used. Sinus hair follicles with a 10 mm length of deep vibrissal nerve attached were microdissected from the whisker pad of animals killed by I.P. and I.C. 3g/kg urethane). Follicles were kept in carbogenated (bubbled medical 95% oxygen, 5% carbon dioxide) synthetic interstitial fluid (SIF). They were slit open lengthways and fixed with insect pins to a silicone elastomer Sylgard platform in a custom-made tissue bath. Capsazepine was made up in SIF and used between 10 - 200 µM. Doses were applied to the preparation at the rate of 1 ml/min for up to 20 min. The two types of units were distinguished by their characteristic static phase firing as previously described (Senok & Baumann, 1997). Statistical analyses included t tests. Capsazepine was tested on a total of 13 St I units. Between 30 - 200 µM caused a transient increase in activity (mean±SEM 52±5 Hz to 80±8 Hz, p < 0.01), notably of the static component. Repeated doses resulted in clear habituation to this excitatory effect. With high concentrations 100 - 200 µM the excitatory effect was followed by a long-lasting and profound depression of all activity (p < 0.01). A total of 15 St II units were studied. Only doses above 50 µM had any effect, and this consisted of a uniform and long-lasting depression of all activity components (dynamic, static and spontaneous) (p < 0.01). In about 25% of St II units which were spontaneously active, a delayed drug effect produced an inversion of response such that ongoing firing was interrupted during the mechanical ramp stimulus. The same effect was only seen in one St I unit. The depression by capsazepine of all activity in both St I and St II units suggest a non-selective effect on mechanoreceptor nerve endings. The excitatory effect of capsazepine that was seen only in St I units may represent an activation of Merkel cells. In another in vitro cell system, capsazepine has been found to increase intracellular calcium (Huang et al, 2006). Pharmacological manipulation (e.g. caffeine (Senok & Baumann, 1997)) which cause calcium influx in Merkel cells results in a selective increase in the static component, as seen here. In conclusion, these results using capsazepine provide weak support for a TRP channel role in St I and St II mechanotransduction. However, the excitatory effect seen in St I mechanoreceptors emphasises their difference from St II mechanoreceptors.

Where applicable, experiments conform with Society ethical requirements